HIV-gp120 affects the functional activity of oligodendrocytes and their susceptibility to complement.
The aim of this study was to assess whether the HIV protein gp120 can induce direct or/and indirect damage to oligodendrocytes (OL). Using highly purified cultures of rat OL, we report that gp120 binds to OL and induces functional alterations in these cells. Indeed, the percentage of cells expressing myelin basic protein (MBP) and the levels of all four MBP isoforms were substantially reduced after a 3-day treatment with 10 nM gp120. As gp120 depressed the ability of OL to reduce the tetrazolium salt MTT (a sign of mitochondrial impairment), the alteration of MBP production may be a consequence of decreased metabolic activity. The above effects were accompanied by a small increase in the number of apoptotic nuclei (from 4.3% in controls to 17.6% in cells treated for 3 days with gp120). As complement can lyse OL and gp120 is known to activate complement, we also studied the interaction between these two factors using OL cultures. The viral protein potentiated (by about 25%) the lytic effect of complement, when administered to the cultures 5 hr after complement, and depressed it (by about 30-40%), when added 5 hr before complement. Heat denaturation and anti-gp120 antibodies prevented the direct effect of gp120 on OL, but did not influence the interactions between gp120 and complement. Some gp120 non glycosylated peptides (V3 loop, 254-274 and 415-435 peptides) mimicked the ability of gp120 to antagonize the lytic effect of complement, but not that of potentiating complement lytic activity. In conclusion, our study indicates that gp120 can alter OL functional activity directly and can interfere with OL susceptibility to complement mediated lysis.
Bernardo
A
A
Laboratory of Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
Agresti
C
C
Levi
G
G
D000818:Animals; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D004676:Myelin Basic Protein / Q000096:biosynthesis*; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D015699:HIV Envelope Protein gp120; D004676:Myelin Basic Protein; D003165:Complement System Proteins